The proposed research employs a mouse model to investigate the effects of cocaine on immune function with an emphasis on possible sex-type differences. The proposal is prompted by: 1) the high incidence of cocaine abuse; 2) the high incidence of AIDS and other infections in cocaine abusers; 3) the absence of a systematic literature on the effects of cocaine on immune function; 4) an even more conspicuous absence of literature on the interactions of cocaine with sex-type and age; and, 5) our preliminary findings that cocaine attenuated Con-A and PHA induced T cell proliferation, the latter at a lower dose in female than male mice. The proposed hypotheses are that acute cocaine exposure will attenuate the immune response; that the attenuation will be greater in female than male mice; that the attenuation will be greater during estrus than diestrus; that the attenuation will be greater in young adult than prepuberal mice; that the gender difference will be greater in young adult than prepuberal mice; and that repeated cocaine injections will produce dose dependent increases in T, B, and NK cell function and decreases in macrophage activity. Our studies will thus systematically examine the effects of varying cocaine dosage and time after drug exposure on the function of T cells, B cells, NK cells, and macrophage in 35-day-old and 60-day-old male and female mice. The proposed studies differ from previous work in several ways. First, the experiments include both male and female mice, thus will establish whether sex-type influences the immune response to cocaine. Use of the two sexes will provide information about whether previous studies completed on males might generalize to females. Second, by including prepuberal and adult groups, the interactions of cocaine, age, and sex-type on immune function will be addressed. Third, the proposed studies provide an initial investigation into the possible influence of estrus state on the effects of cocaine on immune system. Fourth, the study includes dose-response and time course data for both acute and repeated exposure. Finally, four major immunocompetent cell types will be examined under a common exposure condition. This systematic assessment may help resolve some of the conflicting information in extant literature. These studies will fill voids in the basic science literature on the effects of cocaine on immune function particularly in females, and may provide important information relevant to the clinical manifestations of cocaine abuse.